This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 − 194 nm), negative zeta potential (-0.82 to-16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28-49 nm), negative zeta potential (-17 to −27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway.

The objective of this work was to characterize and evaluate wound healing potential of Piper cubeba oil (PO) via selfnanoemulsifying drug delivery system (SNEDDS) in comparison with standard gentamycin. PO loaded SNEDDS was prepared by low energy emulsification technique and characterized for thermodynamic stability, self-emulsification power and various physico-chemical parameters. An optimal formula of PO SNEDDS was subjected to wound healing evaluation, collagen determination and histomorphological examination in female Wistar rats as compared with pure PO and standard antibiotic/gentamycin. An optimal formula of PO SNEDDS showed significant wound healing effects in Wistar female rats in comparison with pure PO. However, wound healing effects of optimized SNEDDS were comparable with standard gentamycin. An optimized formulation also indicated significant enhancement in collagen content (0.82 mg/g) in comparison with pure PO (0.53 mg/g) and negative control (0.33 mg/g). While, the collagen content of SNEDDS (0.82 mg/g) treated rats were comparable with standard gentamycin treated animals (0.98 mg/g). Histopathological examinations of optimized SNEDDS treated animals showed no signs of inflammatory cells which indicated that prepared SNEDDS was safe and nontoxic to rats. The results obtained in this work showed the potential application of SNEDDS in enhancement of the wound healing activity of PO upon oral administration.

The solubility and solution thermodynamic properties of a "bioactive nutraceutical" sinapic acid (SA) in different "2-(2-ethoxyethoxy)ethanol (Carbitol ® ) + water" mixtures were investigated. The "mole fraction solubilities (x e )" of SA in various "Carbitol + water" systems were determined at "T = 298.15-318.15 K" and "p = 0.1 MPa." The measured x e values of SA were found well regressed by "Apelblat, van't Hoff, Yalkowsky, Jouyban-Acree and Jouyban-Acree-van't Hoff" models with mean percent deviations of < 4.0%. The maximum x e value of SA was recorded in pure Carbitol (4.15 × 10 −2 at T = 318.15 K), and the minimum one was estimated in neat water (6.28 × 10 −5 at T = 298.15 K). The regressed results were found to be in accordance with experimental results of SA. Using activity coefficients, mixing thermodynamic parameters of SA were determined. The results showed spontaneous dissolution of SA in most of the cosolvent mixtures.